期刊
JOURNAL OF NEUROSCIENCE
卷 25, 期 1, 页码 130-138出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3764-04.2005
关键词
cyclic nucleotide-gated channel; CNGB1; channel trafficking; rod photoreceptor; retinitis pigmentosa; apoptosis
资金
- NEI NIH HHS [R01 EY014596-03, R01 EY014596, R37 EY006837-15, R01 EY014596-01, R01 EY006837-18, R01 EY006837, R01 EY006837-17, F32 EY006837, R01 EY014596-02, EY 06837, R01 EY006837-16A1, R37 EY006837] Funding Source: Medline
- NIDCD NIH HHS [R01 DC006904-01, R01 DC006904] Funding Source: Medline
Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers composed of homologous A and B subunits. In heterologous expression systems, B subunits alone cannot form functional CNG channels, but they confer a number of channel properties when coexpressed with A subunits. To investigate the importance of the CNGB subunits in vivo, we deleted the CNGB1 gene in mice. In the absence of CNGB1, only trace amounts of the CNGA1 subunit were found on the rod outer segment. As a consequence, the vast majority of isolated rod photoreceptors in mice lacking CNGB1 ( CNGB1(-/-)) failed to respond to light. In electroretinograms (ERGs), CNGB1(-/-) mice showed no rod-mediated responses. The rods also showed a slow-progressing degeneration caused by apoptotic death and concurred by retinal gliosis. Cones were primarily unaffected and showed normal ERG responses up to 6 months, but they started to degenerate in later stages. At the age of similar to1 year, CNGB1(-/-) animals were devoid of both rods and cones. Our results show that CNGB1 is a crucial determinant of native CNG channel targeting. As a result of the lack of rod CNG channels, CNGB1(-/-) mice develop a retinal degeneration that resembles human retinitis pigmentosa.
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